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Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do have are estimated to produce sustained abstinence in less than 20% of individuals. Psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and 2,5-dimethoxy-4-iodoamphetamine (DOI) affect processes related to cognition, perception and sensory processing. Recently, it has been demonstrated that serotonin 5-HT2A receptor agonists, such as psilocybin, can be useful in attenuating substance abuse. As an example, clinical findings have demonstrated the ability of psilocybin to decrease heavy drinking days in alcoholic heavy drinkers. Studies utilizing both rats and mice have also suggested the ability of DOI to decrease ethanol preference and consumption in a two-bottle choice paradigm of drinking behavior. The present study aimed to assess the ability of two acute doses of DOI (2 mg/kg and 5 mg/kg) on ethanol preference and consumption using the two-bottle choice paradigm. To test this, 15 adult male C57BL/6 mice were kept on a reverse light cycle and trained on the two-bottle choice procedure, in which they were allowed to drink for four weeks to obtain a baseline reading of drinking behavior. Following these four weeks, mice were assigned to either the treatment group or vehicle group based on weight and baseline drinking behavior. On the first day of the fifth and sixth weeks, mice were injected intraperitoneally with a dose of DOI or saline vehicle 30 minutes prior to access to 20% ethanol. The amount consumed of both water and ethanol on drinking days was measured at 2- and 24-hours and analyzed to calculate consumption and preference. Overall, our findings suggest that DOI did not affect ethanol consumption or preference at the 2- or 24-hour measures. The DOI-treated group showed no difference from the vehicle-treated group after receiving an either moderate (2 mg/kg) or high (5 mg/kg) dose of DOI. There was an overall interaction of time and treatment in both 2- and 24-hour fluid consumption in the groups. Further studies are warranted using DOI or other psychedelics and other paradigms for assessing drinking behavior to understand the effects of psychedelics in modulating substance use behavior.

Publication Date



alcohol, AUD, psychedelics, SUD, DOI, mice, ethanol, two-bottle choice


Behavioral Neurobiology | Laboratory and Basic Science Research | Pharmacology

Faculty Advisor/Mentor

Javier Gonzalez-Maeso

Is Part Of

VCU Graduate Research Posters

Influence of 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol preference and consumption in C57BL/6 male mice